Inhibiting the P2Y12 Receptor in Megakaryocytes and Platelets Suppresses Interferon-Associated Responses

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2024-09-01 DOI:10.1016/j.jacbts.2024.05.014

Marcin A. Sowa PhD , Haoyu Sun PhD , Tricia T. Wang BA , Vitor W. Virginio PhD , Florencia Schlamp PhD , Hanane El Bannoudi PhD , MacIntosh Cornwell PhD , Hannah Bash BA , Peter M. Izmirly MD , H. Michael Belmont MD , Kelly V. Ruggles PhD , Jill P. Buyon MD , Deepak Voora MD , Tessa J. Barrett PhD , Jeffrey S. Berger MD

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引用次数: 0

Abstract

The authors investigated the impact of antiplatelet therapy on the megakaryocyte (MK) and platelet transcriptome. RNA-sequencing was performed on MKs treated with aspirin or P2Y₁₂ inhibitor, platelets from healthy volunteers receiving aspirin or P2Y₁₂ inhibition, and platelets from patients with systemic lupus erythematosus (SLE). P2Y₁₂ inhibition reduced gene expression and inflammatory pathways in MKs and platelets. In SLE, the interferon (IFN) pathway was elevated. In vitro experiments demonstrated the role of P2Y₁₂ inhibition in reducing IFNα-induced platelet-leukocyte interactions and IFN signaling pathways. These results suggest that P2Y₁₂ inhibition may have therapeutic potential for proinflammatory and autoimmune conditions like SLE.

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抑制巨核细胞和血小板中的 P2Y12 受体可抑制干扰素相关反应

作者研究了抗血小板疗法对巨核细胞（MK）和血小板转录组的影响。研究人员对接受阿司匹林或P2Y12抑制剂治疗的巨核细胞、接受阿司匹林或P2Y12抑制剂治疗的健康志愿者的血小板以及系统性红斑狼疮（SLE）患者的血小板进行了RNA测序。P2Y12 抑制剂减少了 MKs 和血小板中的基因表达和炎症通路。在系统性红斑狼疮中，干扰素（IFN）通路升高。体外实验证明了 P2Y12 抑制剂在减少 IFNα 诱导的血小板-白细胞相互作用和 IFN 信号通路中的作用。这些结果表明，P2Y12 抑制剂可能对系统性红斑狼疮等促炎性和自身免疫性疾病具有治疗潜力。

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.